Women with very high HDL-c levels (≥80 mg/dl) had a 5-fold increased risk of events, 2.5 times higher than men, challenging the "more HDL is better" notion.
Does a high HDL-c profile (≥80 mg/dl) increase the risk of all-cause events and mortality in a normal Southern European population?
Very high HDL-c levels (≥80 mg/dl) are associated with a significantly increased risk of adverse events, particularly in women, challenging the traditional 'more is better' paradigm for HDL-c.
Abstract Background Elevated HDL-c has been associated with increased all-cause mortality in conditions like cancer or liver disease. The traditional "more HDL is better" paradigm is no longer universally accepted. Understanding prognosis is crucial in evaluating cardiovascular and overall risk, especially in women. Aim To investigate the association between HDL-c levels and all causes of events and mortality in a Southern European Population. Methods 1421 normal individuals from a Southern European population (aged 52.2±8.3 years, 73.6% male) were followed during an extended follow-up (mean 7.3±6.0 years). Demographic data, smoking status, alcohol intake, physical activity and clinical risk factors were collected from questionnaires at baseline in 2000. Continuous data were expressed as the mean±SD and compared using the t Student test. Categorical variables were described by percentages and compared using the Chi-square test. The population was stratified into six groups based on HDL-c levels in mg/dl (40, 40 to 49, 50 to 59, 60 to 69, 70 to 79, and ≥80). To investigate the association between HDL-c levels and events, we subdivided each category level into three subgroups (overall population, male and female). In an adjusted multivariate model, Cox regression tested the association between HDL-c levels, all-cause events, and mortality (vascular and non-cardiovascular) adjusted for potential confounders. Results At the end of follow-up, 156 total events were identified (event rate, 15.3 per 1,000 person-years). In the lower category of HDL-c, the general population subgroup and men were significantly associated with an increase in total events compared to the reference group. However, in the highest HDL-c profile (≥80mg/dl), the women have a much higher risk of events (5 times more risk than the reference and approximately 2.5 times above men). Conclusion Our findings highlight the importance of appropriate HDL-c levels in reducing the risk of events and death and challenge the conventional notion that higher HDL-c levels are better. More studies are necessary to clarify whether the associations observed in our study are causal and to elucidate the potential mechanisms.
Sousa et al. (2025) studied this question. Women with very high HDL-c levels (≥80 mg/dl) had a 5-fold increased risk of events, 2.5 times higher than men, challenging the "more HDL is better" notion.